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Eur J Hum Genet. 2014 Sep;22(9):1105-10. doi: 10.1038/ejhg.2014.7. Epub 2014 Feb 5.

Exome sequencing reveals a heterozygous DLX5 mutation in a Chinese family with autosomal-dominant split-hand/foot malformation.

Author information

1
Key Laboratory for Experimental Teratology of the Ministry of Education, Department of Medical Genetics, Shandong University School of Medicine, Jinan, China.
2
Department of Medical Genetics, Linyi People's Hospital, Linyi, China.
3
Department of Orthopedics, Cangshan People's Hospital, Cangshan, China.
4
Department of Biochemistry, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.

Abstract

Split-hand/foot malformation (SHFM) is a congenital limb deformity due to the absence or dysplasia of central rays of the autopod. Six SHFM loci have already been identified. Here we describe a Chinese family with autosomal-dominant SHFM1 that has previously been mapped to 7q21.2-21.3. The two affected family members, mother and son, showed deep median clefts between toes, ectrodactyly and syndactyly; the mother also showed triphalangeal thumbs. Exome sequencing and variant screening of candidate genes in the six loci known to be responsible for SHFM revealed a novel heterozygous mutation, c.558G>T (p.(Gln186His)), in distal-less homeobox 5 (DLX5). As DLX5 encodes a transcription factor capable of transactivating MYC, we also tested whether the mutation could affect DLX5 transcription acitivity. Results from luciferase reporter assay revealed that a mutation in DLX5 compromised its transcriptional activity. This is the first report of a mutation in DLX5 leading to autosomal-dominant SHFM1.

PMID:
24496061
PMCID:
PMC4135423
DOI:
10.1038/ejhg.2014.7
[Indexed for MEDLINE]
Free PMC Article
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